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Biomedical subjects

D Wong

Publications and source records attributed to D Wong.

At least 109 records · Page 6Linked to original sources
PubMed1999

In vitro adhesion and migration of T lymphocytes across monolayers of human brain microvessel endothelial cells: regulation by ICAM-1, VCAM-1, E-selectin and PECAM-1.

Increased lymphocyte traffic across an altered blood-brain barrier (BBB) is a prominent and early event in inflammatory and immune-mediated CNS diseases. The factors that control the entry of lymphocytes into the brain have not been fully elucidated. In this study, primary cultures of human brain microvessel endothelial cells (HBMEC) were used to investigate the role of endothelial cell (EC) adhesion molecules in the adhesion and migration of peripheral blood T lymphocytes across TNF-alpha treated and untreated monolayers. Adhesion of T cells to unstimulated HBMEC was minimal and few of the adherent cells migrated across the monolayers. Treatment of HBMEC with TNF-alpha augmented adhesion by 5-fold. The binding to activated EC was significantly, but not completely, inhibited by monoclonal antibodies (mAbs) to ICAM-1 and VCAM-1, whereas adhesion to unstimulated EC was blocked by mAb to ICAM-1 but not VCAM-1. Transendothelial migration of lymphocytes increased by up to 30-fold following treatment of HBMEC with TNF-alpha. Migration across activated monolayers, but not across untreated EC, was almost completely blocked by Ab to ICAM-1 and significantly inhibited by Abs to PECAM-1 and E-selectin. VCAM-1 was not utilized during transendothelial migration. Ultrastructurally, pseudopodia from lymphocytes contacted finger-like cytoplasmic projections on EC and eventually penetrated the EC cytoplasm at focal points along the apical surface. Migrating lymphocytes moved either through the EC cytoplasm or between adjacent EC across intercellular contacts. The overlying monolayers showed no evidence of disruption and intercellular junctions appeared intact over the migrated T cells. These studies indicate that adhesion and migration of T lymphocytes across the cerebral endothelial barrier are distinct processes that depend upon the activation state of EC and are controlled by diverse receptor-ligand interactions.

Blood-Brain Barrier↗
PubMed1999

Cortical representation of spatiotemporal pattern of firing evoked by echolocation signals: population encoding of target features in real time.

Target perception in echolocating bats entails the generation of an acoustic image of the target in the auditory cortex. By integrating information conveyed in the sequence of acoustic echoes, the population of cortical neurons in hypothesized to encode different target features based on its spatiotemporal pattern of neural-spike firing during the course of echolocation. A biologically plausible approach to the cortical representation of target features is employed by using electrophysiological data recorded from the auditory cortex of the FM bat, Myotis lucifugus. A single-neuron model of delay-sensitive neurons is first approximated by the formulation of a Gaussian function with different variables to represent the delay-tuning properties of individual cortical neurons. A cortical region consisting of delay-sensitive neurons organized topographically according to best frequency (i.e., tontopically organized) is then modeled with multiple layers of the single-neuron model. A mechanism is developed to represent and encode the responses of these neurons based on time-dependent, incoming echo signals. The time-varying responses of the population of neurons are mapped spatially on the auditory-cortical surface as a cortical response map (CORMAP). The model is tested using phantom targets with single and multiple glints. These simulation results provide further validation of the current auditory framework as a biomimetic mechanism for capturing time-varying, acoustic stimuli impinging in the bat's ears, and the neural representation of acoustic stimulus features by saptiotemporal-firing patterns in the cortical population.

Auditory Cortex↗
PubMed1999

Trends in vitreoretinal surgery at a tertiary referral centre: 1987 to 1996.

AIM: To identify trends in vitreoretinal surgery at a tertiary referral centre from 1987 to 1996. METHODS: A retrospective study of patients who had undergone vitreoretinal surgery at St Paul's Eye Unit over two 6 month periods in 1987 and 1996. Preoperative ocular status, surgery details, and outcome were collected. chi 2 and Mann-Whitney U tests were used to analyse the data. RESULTS: The two periods under study were July to December 1987 and January to June 1996. 110 operations performed during 1987 (96 patients) and 330 operations during 1996 (289 patients) were analysed. There was a fourfold rise in the number of tertiary referrals and a seven-fold rise in the number of operations performed for conditions other than rhegmatogenous retinal detachment (RRD). Increasing indications for surgery included diabetic eye disease, macular hole, dropped nucleus, endophthalmitis, and subretinal neovascular membrane. There was a rise in the proportion of patients with RRD following cataract surgery (from 19.5% to 29.5%). For both primary repair and reoperation, vitrectomy with internal tamponade was more commonly used in 1996. The anatomical success rate for primary repair changed from 76.6% to 84.7% after one operation and from 89.1% to 94.3% following additional surgery. CONCLUSIONS: This study points to a trend towards subspecialisation and tertiary referral in vitreoretinal surgery. Vitrectomy techniques are more commonly used for the primary repair of RRD and are applied to a wider spectrum of diseases.

Humans↗
PubMed1999

Effect of induced metabolic acidosis on human skeletal muscle metabolism during exercise.

The roles of pyruvate dehydrogenase (PDH), glycogen phosphorylase (Phos), and their regulators in lactate (Lac(-)) metabolism were examined during incremental exercise after ingestion of 0.3 g/kg of either NH(4)Cl [metabolic acidosis (ACID)] or CaCO(3) [control (CON)]. Subjects were studied at rest, at rest postingestion, and during continuous steady-state cycling at three stages (15 min each): 30, 60, and 75% of maximal oxygen uptake. Radial artery and femoral venous blood samples, leg blood flow, and biopsies of the vastus lateralis were obtained during each power output. ACID resulted in significantly lower intramuscular concentration of [Lac(-)] (ACID 40.8 vs. CON 56.9 mmol/kg dry wt), arterial whole blood [Lac(-)] (ACID 4.7 vs. CON 6.5 mmol/l), and leg Lac(-) efflux (ACID 3.05 vs. CON 6.98 mmol. l(-1). min(-1)). The reduced intramuscular [Lac(-)] resulted from decreases in pyruvate production due to inhibition of glycogenolysis, at the level of Phos a, and phosphofructokinase, together with an increase in the amount of pyruvate oxidized relative to the total produced. The reduction in Phos a activity was mediated through decreases in transformation, decreases in free inorganic phosphate concentration, and decreases in the posttransformational allosteric regulator free AMP. Reduced PDH activity occurred with ACID and may have resulted from alterations in the concentrations of acetyl-CoA, free ADP, pyruvate, NADH, and H(+), leading to greater relative activity of the kinase. The results demonstrate that imposed metabolic acidosis in skeletal muscle results in decreased Lac(-) production due to inhibition of glycogenolysis at the level of Phos and increased pyruvate oxidation at PDH.

Acidosis↗
PubMed1999

Prevalence of antibodies to the hepatitis E virus in pigs from countries where hepatitis E is common or is rare in the human population.

Hepatitis E virus (HEV) is a very important public health concern in many developing countries where epidemics of hepatitis E are common. Sporadic cases of clinical hepatitis E not only occur in these countries but also occur uncommonly in patients with no known epidemiological exposure to HEV in industrialized countries. The source of infection in industrialized countries is unknown but it has been suggested that animals might serve as a reservoir for HEV in both settings. We recently identified and characterized an HEV strain (swine HEV) that infects large numbers of pigs in the United States. To assess the potential of pigs to serve as a global reservoir of HEV, we measured the prevalence of HEV antibodies in pigs in two countries where hepatitis E is endemic and two countries where it is not. Swine herds in all four countries contained many pigs that were seropositive for IgG anti-HEV, although the percentage of seropositive pigs varied greatly from herd to herd. A very limited number of pig handlers in the two endemic countries were also tested and most of them were found to be seropositive for HEV. The results from this study suggest that hepatitis E is enzootic in pigs regardless of whether HEV is endemic in the respective human population. J. Med. Virol. 59:297-302, 1999. Published 1999 Wiley-Liss, Inc.

Age Factors↗
PubMed1999

Positron emission tomography in cochlear implant and auditory brain stem implant recipients.

OBJECTIVE: The purpose of this study was to determine whether similar cortical regions are activated by speech signals in profoundly deaf patients who have received a multichannel cochlear implant (CI) or auditory brain stem implant (ABI) as in normal-hearing subjects. STUDY DESIGN: Positron emission tomography (PET) studies were performed using a variety of discrete stimulus conditions. Images obtained were superimposed on standard anatomic magnetic resonance imaging (MRI) for the CI subjects. The PET images were superimposed on the ABI subject's own MRI. SETTING: Academic, tertiary referral center. PATIENTS: Five subjects who have received a multichannel CI and one who had received an ABI. INTERVENTION: Multichannel CI and ABI. MAIN OUTCOME MEASURE: PET images. RESULTS: Similar cortical regions are activated by speech stimuli in subjects who have received an auditory prosthesis. CONCLUSIONS: Neuroimaging provides a new approach to the study of speech processing in CI and ABI subjects.

Acoustic Stimulation↗
PubMed1999

Adenocarcinoma of the head of the pancreas: effects of surgical and nonsurgical therapy on survival--a ten-year experience.

A retrospective analysis of all patients treated for adenocarcinoma of the head of the pancreas from 1989 to 1998 was performed. Excluded were cancers in the body and tail, cystic neoplasms, ampullary tumors, and cancers of the duodenum and bile ducts. One hundred forty-five patients were reviewed, and 43 patients underwent pancreaticoduodenectomy. Data collected included the stage, lymph node status, surgical margins, adjuvant therapies, and survival. Statistical analysis was performed with Cox's Proportional Hazards Analysis and Log-Rank Life Table Analysis. The surgical population had a 21 per cent 3-year survival rate and a 7 per cent operative mortality rate. Median survival was: 1) the resection group versus no resection was 13.5 versus 3.1 months; 2) adjuvant therapy versus no therapy after resection was 16.1 versus 5.1 months; and 3) chemoradiation therapy versus no therapy for unresectable disease was 5.3 versus 1.8 months. The presence of positive surgical margins was found in 33 per cent of the surgical specimens and carried an increased mortality hazard ratio of 3.1. Patients with negative lymph nodes had a 15 per cent 5-year survival, versus 0 per cent with positive nodes. Seventy-three per cent of those resected had a T2 lesion, and 46 per cent of patients presented with metastatic disease. Surgical resection and adjuvant therapy significantly improves survival in patients with adenocarcinoma of the head of the pancreas. All patients who underwent resection as part of their therapy showed extended survival compared with chemoradiation therapy alone. Adjuvant chemoradiation improved survival when compared with surgery alone. Multimodality treatment in carcinoma of the head of the pancreas provides the best treatment option. However, better adjuvant therapies are needed.

Adenocarcinoma↗
PubMed1998

First African-American child with juvenile neuronal ceroid lipofuscinosis.

The neuronal ceroid lipofuscinoses are among the most common forms of progressive neurodegenerative disease of childhood. They appear to be panethnic, but there is a special predilection of the infantile subtype in Finland. In the United States, the Batten disease registry of 731 cases shows that juvenile neuronal ceroid lipofuscinosis (JNCL) is the most common form. Here, we report on the first known African-American child with JNCL. Genetic study showed the 1.02-kb deletion typically seen in JNCL cases.

Black People↗
PubMed1998

Spinal epidural abscess.

AIMS: To review the clinical presentation and outcome of patients with spinal epidural abscess. METHODS: Following an index case, additional cases were identified during 1991-6. RESULTS: There were a total of seven patients with spinal epidural abscess and an average age of 52 years (range 24-75 years). The abscess locations were cervical (3), thoracic (3) or thoracolumbar (1), and extended on average 4.3 vertebral bodies (range 2-9). Staphylococcus aureus was the aetiologic agent in all of the six microbiologically confirmed cases. Three abscesses arose from adjacent vertebral osteomyelitis, one followed epidural anaesthesia and two arose by haematogenous spread. New spinal or radicular pain were the most frequent early symptoms, later, nerve root weakness or a sensory level. An ESR > 30 mm/hour was consistently present but fever and leukocytosis were absent in some patients. MRI (five cases) and myelography (one case) were diagnostic. Five patients underwent laminectomy and abscess drainage; in three, limb weakness improved markedly post operatively. Three of the four patients with paralysis died, two despite laminectomy. CONCLUSIONS: New spinal pain, radicular symptoms or signs, and a raised ESR were the most consistent early abnormalities in patients with a spinal epidural abscess. Diagnosis at an early clinical stage was associated with a better outcome.

Abscess↗
PubMed1998

Isoform-specific effects of human apolipoprotein E on brain function revealed in ApoE knockout mice: increased susceptibility of females.

Apolipoprotein E (apoE) mediates the redistribution of lipids among cells and is expressed at highest levels in brain and liver. Human apoE exists in three major isoforms encoded by distinct alleles (epsilon2, epsilon3, and epsilon4). Compared with APOE epsilon2 and epsilon3, APOE epsilon4 increases the risk of cognitive impairments, lowers the age of onset of Alzheimer's disease (AD), and decreases the response to AD treatments. Besides age, inheritance of the APOE epsilon4 allele is the most important known risk factor for the development of sporadic AD, the most common form of this illness. Although numerous hypotheses have been advanced, it remains unclear how APOE epsilon4 might affect cognition and increase AD risk. To assess the effects of distinct human apoE isoforms on the brain, we have used the neuron-specific enolase (NSE) promoter to express human apoE3 or apoE4 at similar levels in neurons of transgenic mice lacking endogenous mouse apoE. Compared with NSE-apoE3 mice and wild-type controls, NSE-apoE4 mice showed impairments in learning a water maze task and in vertical exploratory behavior that increased with age and were seen primarily in females. These findings demonstrate that human apoE isoforms have differential effects on brain function in vivo and that the susceptibility to apoE4-induced deficits is critically influenced by age and gender. These results could be pertinent to cognitive impairments observed in human APOE epsilon4 carriers. NSE-apoE mice and similar models may facilitate the preclinical assessment of treatments for apoE-related cognitive deficits.

Age Factors↗
PubMed1998

Pitch processing in the human brain is influenced by language experience.

Positron emission tomography (PET) was used in a cross-linguistic study to compare pitch processing in native speakers of English, a nontone language, with those of Thai, a tone language. When discriminating pitch patterns in Thai words, only the Thai subjects showed activation in the left frontal operculum. Activation of this region near the classically defined Broca's area suggests that the brain recognizes functional properties, rather than simply acoustic properties, of complex auditory cues in accessing language-specific mechanisms in pitch perception.

Acoustic Stimulation↗
PubMed1998

Amyloid protein precursor stimulates excitatory amino acid transport. Implications for roles in neuroprotection and pathogenesis.

Excitatory neurotransmitters such as glutamate are required for the normal functioning of the central nervous system but can trigger excitotoxic neuronal injury if allowed to accumulate to abnormally high levels. Their extracellular levels are controlled primarily by transmitter uptake into astrocytes. Here, we demonstrate that the amyloid protein precursor may participate in the regulation of this important process. The amyloid protein precursor has been well conserved through evolution, and a number of studies indicate that it may function as an endogenous excitoprotectant. However, the mechanisms underlying this neuroprotective capacity remain largely unknown. At moderate levels of expression, human amyloid protein precursors increased glutamate/aspartate uptake in brains of transgenic mice, with the 751-amino acid isoform showing greater potency than the 695-amino acid isoform. Cerebral glutamate/aspartate transporter protein levels were higher in transgenic mice than in non-transgenic controls, whereas transporter mRNA levels were unchanged. Amyloid protein precursor-dependent stimulation of aspartate uptake by cultured primary astrocytes was associated with increases in protein kinase A and C activity and could be blocked by inhibitors of these kinases. The stimulation of astroglial excitatory amino acid transport by amyloid protein precursors could protect the brain against excitotoxicity and may play an important role in neurotransmission.

Amyloid beta-Protein Precursor↗
PubMed1998

Structure/function analyses of recombinant variants of human factor Xa: factor Xa incorporation into prothrombinase on the thrombin-activated platelet surface is not mimicked by synthetic phospholipid vesicles.

This report describes the expression, purification, and characterization of a series of recombinant factor Xa variants bearing aspartate substitutions for each of the glutamate residues which normally undergo gamma-carboxylation. Factor X was expressed in human embryonic kidney cells and purified from conditioned media by immunoaffinity and hydroxylapatite chromatography. Factor X was activated with Russell's viper venom factor X activator, and single-chain unactivated factor X was removed from activated factor X by size-exclusion chromatography. Recombinant wild-type factor Xa had normal activity in a clotting assay, and mutants with aspartate substitutions for glas residues 16, 26, and 29 had no detectable clotting activity. In purified component assays, these gla variants had essentially no detectable activity in the prothrombinase complex assembled on synthetic phospholipid vesicles but had significant activity when the prothrombinase was assembled on thrombin-activated platelets. In addition, the gla 32 variant had normal activity in the platelet prothrombinase but diminished activity in prothrombinase assembled on synthetic PSPC vesicles. These differences were not accounted for by the total phospholipid composition of the thrombin-activated platelet membrane. We have produced fully active recombinant human factor Xa and demonstrated that gla residues 16, 26, and 29 are critical for normal activity of factor Xa. More importantly, this study provides an extensive characterization of macromolecular enzyme complex formation with gla variants of a vitamin K-dependent coagulation protein and provides evidence that prothrombinase complex assembly on thrombin-activated platelets is not equivalent to assembly on synthetic phospholipid vesicles. The data suggest that thrombin-activated platelets possess some element(s) (other than 30% phosphatidyl serine or factor Va), presumably either protein or phospholipid, that serves as a component of the factor Xa binding site.

Blood Coagulation↗
PubMed1998

Exchange of perfluorodecalin for gas or oil: a model for avoiding slippage.

BACKGROUND: The introduction of liquid perfluorocarbons as an intraoperative tool has greatly facilitated retinal re-apposition in giant retinal tears (GRT) and relieving retinotomies (RR). Slippage of the retina can occur during the exchange of heavy liquids for oil or gas, especially if the fill of perfluorocarbons is subtotal. METHODS: We have used a model eye chamber to study the surface interactions of perfluorodecalin (PFD) with silicone oil and air to evaluate possible mechanisms of slippage. RESULTS: The results demonstrate that it is possible during a PFD/air exchange to trap a wedge of aqueous which is displaced laterally and forced posteriorly during removal of the PFD, whereas during a PFD/silicone oil exchange the remaining aqueous is displaced laterally and upwards and thus trapped above the silicone oil/PFD interface. CONCLUSIONS: We believe that during PFD/air exchange the displacement of the aqueous posteriorly can cause slippage and that this could be avoided by performing a direct PFD/silicone oil exchange.

Air↗
PubMed1998

Visual function and patient satisfaction after macular hole surgery.

PURPOSE: Over recent years success in macular hole surgery has increased in terms of anatomical closure. However, debate still continues on the benefit to the patient in terms of visual outcome. We designed a prospective study to investigate the outcome of full thickness macular hole (FTMH) surgery in terms of anatomical closure, visual outcome, incidence of complications and patient satisfaction. METHODS: Thirty eyes of 30 consecutive patients with FTMH were prospectively studied (stage 2 = 2; stage 3 = 23; stage 4 = 5). All cases had surgery involving vitrectomy, injection of an autologous platelet aggregate over the hole and gas tamponade. At 3 months post-operatively all cases were assessed for closure of the FTMH, Snellen acuity and the incidence of complications. At this stage all patients completed a patient satisfaction questionnaire. RESULTS: Anatomical closure of the hole was achieved in 83% of cases (25/30). Visual improvement of 2 Snellen lines or more occurred in 50% of cases (15/30). A vision of 6/12 or better was achieved in 27% of cases (8/30). A post-operative lens opacity was present in 46% (13/28) of phakic patients and a temporal, peripheral wedge-shaped field defect occurred in 17% (5/30) of cases. In this study, 53%, 70%, 57% and 67% of patients gave a positive response to specific questions about satisfaction with near, intermediate and distance vision and overall visual function respectively. CONCLUSIONS: Although the anatomical success of FTMH surgery is high the functional outcome in terms of Snellen acuity is less rewarding. Analysis of patient satisfaction suggests that the arbitrary visual outcome measures presently used may underestimate the functional benefit to the patient. Improved objective measures of visual outcome are required to assess the benefit of surgery in these cases.

Aged↗